CLONING, PARENTHOOD, AND GENETIC RELATEDNESS

In this paper I examine what I take to be the best case for reproductive human cloning, as a medical procedure designed to overcome infertility, and argue that it founders on an irresolvable tension in the attitude towards the importance of being ‘genetically related’ to our children implied in the desire to clone. Except in the case where couples are cloning a child they have previously conceived naturally, cloning is unable to establish the right sort of genetic relation to make couples the parents of their cloned child. If anybody is the genetic parent of a cloned child it is the natural parent(s) of the DNA donor. Paradoxically, in order to resist the claims of the parents of the donor to the cloned child, the argument for human reproductive cloning must place more weight on the intention to parent a child, than we do in cases of ordinary reproduction. It must insist that the parental relation is established by the intentions of the couple who bring a clone into the world and not by their genetic relation to the child. The emphasis placed on intention as establishing the parental relationship works to undermine the justification for cloning in the first place. For cloning to play a useful role as a reproductive technology, it must allow couples to become parents who could do so no other way. However, to the extent that intention is sufficient to establish parenthood, adoption or surrogacy, which are existing alternatives to cloning, will serve equally well to allow couples to become parents.     

In vitro gametogenesis and reproductive cloning: Can we allow one while banning the other?

In vitro gametogenesis (IVG) is believed to be the next big breakthrough in reproductive medicine. The prima facie acceptance of this possible future technology is notable when compared to the general prohibition on human reproductive cloning. After all, if safety is the main reason for not allowing reproductive cloning, one might expect a similar conclusion for the reproductive application of IVG, since both technologies hold considerable and comparable risks. However, safety concerns may be overcome, and are presumably not the sole reason why cloning is being condemned. We therefore assess the non‐safety arguments against reproductive cloning, yet most of these can also be held against IVG. The few arguments that cannot be used against IVG are defective. We conclude from this that it will be hard to defend a ban on reproductive cloning while accepting the reproductive use of IVG.     

Cloning and adoption: a reply to Levy and Lotz

In previous articles I discussed the ethics of human reproductive cloning, focusing on a possible future scenario in which reproductive cloning can be accomplished without an elevated risk of anomalies to the children who are created. I argued that in such a scenario it would be ethically permissible for infertile couples to use cloning as a way to have genetically related children and that such use should not be prohibited. In 'Reproductive Cloning and a (Kind of) Genetic Fallacy', Neil Levy and Mianna Lotz raise objections to my conclusions. They disagree with the view, for which I argued, that some couples can have defensible reasons for desiring genetically related children. They also offer several new arguments against reproductive cloning, including an argument that it would diminish the number of adoptions, thereby adversely affecting the welfare of children who need to be adopted. In this paper I point out that Levy and Lotz's criticisms misconstrue my arguments and that there are serious problems with their arguments for prohibiting infertile couples from using cloning, including their argument from adoption.     

Human cloning: category, dignity, and the role of bioethics

Human cloning has been simultaneously a running joke for massive worldwide publicity of fringe groups like the Raelians, and the core issue of an international movement at the United Nations in support of a treaty to ban the use of cloning techniques to produce a child (so called reproductive cloning). Yet, even though debates on human cloning have greatly increased since the birth of Dolly, the clone sheep, in 1997, we continue to wonder whether cloning is after all any different from other methods of medically assisted reproduction, and what exactly makes cloning an 'affront to the dignity of humans.' Categories we adopt matter mightily as they inform but can also misinform and lead to mistaken and unproductive decisions. And thus bioethicists have a responsibility to ensure that the proper categories are used in the cloning debates and denounce those who try to win the ethical debate through well-crafted labels rather than well-reasoned argumentations. But it is as important for bioethicists to take a position on broad issues such as human cloning and species altering interventions. One 'natural question' would be, for example, should there be an international treaty to ban human reproductive cloning?     

Heterochronic expression of sexual reproductive programs during apomictic development in Tripsacum

Some angiosperms reproduce by apomixis, a natural way of cloning through seeds. Apomictic plants bypass both meiosis and egg cell fertilization, producing progeny that are genetic replicas of the mother plant. In this report, we analyze reproductive development in Tripsacum dactyloides, an apomictic relative of maize, and in experimental apomictic hybrids between maize and Tripsacum. We show that apomictic reproduction is characterized by an alteration of developmental timing of both sporogenesis and early embryo development. The absence of female meiosis in apomictic Tripsacum results from an early termination of female meiosis. Similarly, parthenogenetic development of a maternal embryo in apomicts results from precocious induction of early embryogenesis events. We also show that male meiosis in apomicts is characterized by comparable asynchronous expression of developmental stages. Apomixis thus results in an array of possible phenotypes, including wild-type sexual development. Overall, our observations suggest that apomixis in Tripsacum is a heterochronic phenotype; i.e., it relies on a deregulation of the timing of reproductive events, rather than on the alteration of a specific component of the reproductive pathway.     

Genetic counselling. I. Definition and present status (author's transl)]

Genetic counselling is a medical action which must be carried out by a M.D. specialized in genetics. Genetic counselling is peculiar in that couples rather than individuals are involved. Furthermore it is not concerned with the health of the consultants but with that of their expected children. Genetic counselling is not restricted to the statistical estimation of a risk; it raises important problems of psychology and behaviour. Finally, eugenic considerations about the diffusion of deleterious genes should not be taken into account in genetic counselling, which is given in the interest of individuals, not of the society. The increasing demand for genetic counselling is due to the change of the reproductive pattern. People do not want only to fix the size of their family, but also to avoid any accident of procreation.     

Safety, identity and consent: a limited defense of reproductive human cloning

Some opponents of reproductive human cloning have argued that, because of its experimental nature, any attempt to create a child by way of cloning would risk serious birth defects or genetic abnormalities and would therefore be immoral. Some versions of this argument appeal to the consent of the person to be conceived in this way. In particular, they assume that if an experimental reproductive technology has not yet been shown to be safe, then, before we use it, we are morally obligated to get either the actual consent or the presumed consent of the person to be conceived. In this article, I attempt to explain the appeal of such consent-based arguments as deriving from a mistaken view of personal identity. I then argue that since this view is false, such arguments are unsound. Finally, I argue that even if reproductive cloning is unsafe, it may still be morally permissible in some circumstances.     

Longitudinal Study of Reproductive Performance of Female Cattle Produced by Somatic Cell Nuclear Transfer

The objective of this study was to determine whether or not reproductive performance in cattle produced by somatic cell nuclear transfer (SCNT) is significantly different from that of their genetic donors. To address this question, we directed two longitudinal studies using different embryo production procedures: (1) superovulation followed by artificial insemination (AI) and embryo collection and (2) ultrasound-guided ovum pick-up followed by in vitro fertilization (OPU-IVF). Collectively, these two studies represent the largest data set available for any species on the reproductive performance of female clones and their genetic donors as measured by their embryo production outcomes in commercial embryo production program. The large-scale study described herein was conducted over a six-year period of time and provides a unique comparison of 96 clones to the 40 corresponding genetic donors. To our knowledge, this is the first longitudinal study on the reproductive performance of cattle clones using OPU-IVF. With nearly 2,000 reproductive procedures performed and more than 9,200 transferable embryos produced, our observations show that the reproductive performance of cattle produced by SCNT is not different compared to their genetic donors for the production of transferable embryos after either AI followed by embryo collection (P = 0.77) or OPU-IVF (P = 0.97). These data are in agreement with previous reports showing that the reproductive capabilities of cloned cattle are equal to that of conventionally produced cattle. In conclusion, results of this longitudinal study once again demonstrate that cloning technology, in combination with superovulation, AI and embryo collection or OPU-IVF, provides a valuable tool for faster dissemination of superior maternal genetics.     

Developmental genetics of gametophytic apomixis

Some higher plants reproduce asexually by apomixis, a natural way of cloning through seeds. Apomictic plants produce progeny that are an exact genetic replica of the mother plant. The replication is achieved through changes in the female reproductive pathway such that female gametes develop without meiosis and embryos develop without fertilization. Although apomixis is a complex developmental process, genetic evidence suggests that it might be inherited as a simple mendelian trait - a paradox that could be explained by recent data derived from apomictic species and model sexual organisms. The data suggest that apomixis might rely more on a global deregulation of sexual reproductive development than on truly new functions, and molecular mechanisms for such a global deregulation can be proposed. This new understanding has direct consequences for the engineering of apomixis in sexual crop species, an application that could have an immense impact on agriculture.     

The ethics of therapeutic and reproductive human cloning.

Neither therapeutic cloning nor reproductive cloning necessarily pose insurmountable ethical obstacles. Two defences of therapeutic cloning are considered. The first defence, the argument from property, is rejected because it entails morally counter-intuitive consequences. We should prefer a 'balance of reasons' defence which leaves room for the view that human life has intrinsic value. Reproductive cloning is best defended by an appeal to the right to procreative autonomy. The sorts of harms it is feared clones will suffer are also suffered by children conceived through natural means, even when these harms were preventable. The right to reproductive autonomy disallows state control of any form of reproduction for the reasons of child welfare discussed.     

ORPHANS BY DESIGN: THE FUTURE OF GENETIC PARENTHOOD

Establishing the nature of genetic parenthood is an important task. This is, firstly, because many people desire that relationship and it is in their interest to know what that is, and secondly, because there is a view that it may incur certain moral obligations between the genetic parent and their child. Many theorists have made attempts to define exactly what genetic parenthood is. I show that these definitions are deficient if they wish to fully capture all reproductive scenarios in ways that are intuitive and/or meaningful. Through a series of cases involving technologies such as cloning and genome editing, we see that in lieu of the traditional two parents, there are possible beings who have no genetic parents, one genetic parent, or many genetic parents. Establishing these cases complicates our understanding of genetic parenthood. From this, we must reconsider current definitions, as well as the usefulness of defining genetic parenthood in these complex cases. Here I do not aim to establish a new definition, but rather to suggest that this complexity makes it necessary to re‐assess the importance of the connection between genetic parenthood and parental obligations and authorities.     

Procreative beneficence: why we should select the best children

Eugenic selection of embryos is now possible by employing in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). While PGD is currently being employed for the purposes of detecting chromosomal abnormalities or inherited genetic abnormalities, it could in principle be used to test any genetic trait such as hair colour or eye colour.
Genetic research is rapidly progressing into the genetic basis of complex traits like intelligence and a gene has been identified for criminal behaviour in one family. Once the decision to have IVF is made, PGD has few 'costs' to couples, and people would be more inclined to use it to select less serious medical traits, such as a lower risk of developing Alzheimer Disease, or even for non-medical traits. PGD has already been used to select embryos of a desired gender in the absence of any history of sex-linked genetic disease.
I will argue that: (1) some non-disease genes affect the likelihood of us leading the best life; (2) we have a reason to use information which is available about such genes in our reproductive decision-making; (3) couples should select embryos or fetuses which are most likely to have the best life, based on available genetic information, including information about non-disease genes. I will also argue that we should allow selection for non-disease genes even if this maintains or increases social inequality. I will focus on genes for intelligence and sex selection.
I will defend a principle which I call Procreative Beneficence: couples (or single reproducers) should select the child, of the possible children they could have, who is expected to have the best life, or at least as good a life as the others, based on the relevant, available information.     

Will knowledge of human genome variation result in changing cancer paradigms?

Our incomplete understanding of carcinogenesis may be a significant reason why some cancer mortality rates are still increasing. This lack of understanding is likely due to a research approach that relies heavily on genetic comparison between cancerous and non-cancerous tissues and cells, which has led to the identification of genes of cancer proliferation rather than differentiation. Recent observations showing that a tremendous degree of natural human genetic variation occurs are likely to lead to a shift in the basic paradigms of cancer genetics, in that there is a need to consider both the nature of the genes involved, and the idea that not every genetic variation identified in these genes may be associated with carcinogenesis. Based on studies using LCM and micro-genetic analyses, we propose that significant cancer initiating events may take place during the very early stages of development of cancer-susceptible tissues and that using such techniques might greatly help us in our understanding of carcinogenesis.     

Biotechnology in reproductive medicine

In this review I am summarizing the past and current progress in the field of pharmaceutical, diagnostic, therapeutic, and reproductive cloning in mammals. Several human gene products can be pharmaceutically explored in transgenic farm animals and employed for medical applications. Preimplantation genetic diagnosis (PGD) is utilizing modern molecular cloning techniques to detect genetic and chromosomal aberrations in early embryos originating from patients with inborn errors at risk for hereditary diseases or age-related risk for abnormal karyotype. Stem cell engineering from early human embryos is creating new and promising but also controversial applications for therapeutic and regenerative medicine. Potential risk factors for reproductive cloning are presented and discussed in the context of possible developmental malformations, frequently observed after embryo culture and cloning in farm animals. Future extension of biotechnology to human reproductive cloning is currently under worldwide dispute.     

Designing humans: A human rights approach

Advances in genomic technologies such as CRISPR‐Cas9, mitochondrial replacement techniques, and in vitro gametogenesis may soon give us more precise and efficient tools to have children with certain traits such as beauty, intelligence, and athleticism. In this paper, I propose a new approach to the ethics of reproductive genetic engineering, a human rights approach. This approach relies on two claims that have certain, independent plausibility: (a) human beings have equal moral status, and (b) human beings have human rights to the fundamental conditions for pursuing a good life. I first argue that the human rights approach gives us a lower bound of when reproductive genetic engineering would be permissible. I then compare this approach with other approaches such as the libertarian, perfectionist, and life worth living approaches. Against these approaches, I argue that the human rights approach offers a novel, and more plausible, way of assessing the ethics of reproductive genetic engineering.     

Extreme genetic differences between queens and workers in hybridizing Pogonomyrmex harvester ants

The process of reproductive caste determination in eusocial insect colonies is generally understood to be mediated by environmental, rather than genetic factors. We present data demonstrating unexpected genetic differences between reproductive castes in a variant of the rough harvester ant, Pogonomyrmex rugosus var. fuscatus. Across multiple loci, queens were consistently more homozygous than expected, while workers were more heterozygous. Adult colony queens were divided into two highly divergent genetic groups, indicating the presence of two cryptic species, rather than a single population. The observed genetic differences between castes reflect differential representation of heterospecific and conspecific patrilines in these offspring groups. All workers were hybrids; by contrast, winged queens were nearly all pure-species. The complete lack of pure-species workers indicates a loss of worker potential in pure-species female offspring. Hybrids appear to be bipotential, but do not normally develop into reproductives because they are displaced by pure-species females in the reproductive pool. Genetic differences between reproductive castes are expected to be rare in non-hybridizing populations, but within hybrid zones they may be evolutionarily stable and thus much more likely to occur.     

HUMAN REPRODUCTIVE CLONING: A CONFLICT OF LIBERTIES

Proponents of human reproductive cloning do not dispute that cloning may lead to violations of clones' right to self-determination, or that these violations could cause psychological harms. But they proceed with their endorsement of human reproductive cloning by dismissing these psychological harms, mainly in two ways. The first tactic is to point out that to commit the genetic fallacy is indeed a mistake; the second is to invoke Parfit's non-identity problem. The argument of this paper is that neither approach succeeds in removing our moral responsibility to consider and to prevent psychological harms to cloned individuals. In fact, the same commitment to personal liberty that generates the right to reproduce by means of cloning also creates the need to limit that right appropriately. Discussion of human reproductive cloning ought to involve a careful and balanced consideration of both the relevant aspects of personal liberty – the parents' right to reproductive freedom and the cloned child's right to self-determination.     

Genetic variation in gorillas

This review summarizes what is currently known concerning genetic variation in gorillas, on both inter- and intraspecific levels. Compared to the human species, gorillas, along with the other great apes, possess greater genetic variation as a consequence of a demographic history of rather constant population size. Data and hence conclusions from analysis of mitochondrial DNA (mtDNA), the usual means of describing intraspecific patterns of genetic diversity, are limited at this time. An important task for future studies is to determine the degree of confidence with which gorilla mtDNA can be analyzed, in view of the risk that one will inadvertently analyze artifactual rather than genuine sequences. The limited information available from sequences of nuclear genomic segments does not distinguish western from eastern gorillas, and, in comparison with results from the two chimpanzee species, suggests a relatively recent common ancestry for all gorillas. In the near future, the greatest insights are likely to come from studies aimed at genetic characterization of all individual members of social groups. Such studies, addressing topics such as behavior of individuals with kin and non-kin, and the actual success of male reproductive strategies, will provide a link between behavioral and genetic studies of gorillas.     

Donor cell differentiation,reprogramming, and cloning efficiency: Elusive or illusive correlation?

Compared to other assisted reproductive technologies, mammalian nuclear transfer (NT) cloning is inefficient in generating viable offspring. It has been postulated that nuclear reprogramming and cloning efficiency can be increased by choosing less differentiated cell types as nuclear donors. This hypothesis is mainly supported by comparative mouse cloning experiments using early blastomeres, embryonic stem (ES) cells, and terminally differentiated somatic donor cells. We have re-evaluated these comparisons, taking into account different NT procedures, the use of donor cells from different genetic backgrounds, sex, cell cycle stages, and the lack of robust statistical significance when post-blastocyst development is compared. We argue that while the reprogrammability of early blastomeres appears to be much higher than that of somatic cells, it has so far not been conclusively determined whether differentiation status affects cloning efficiency within somatic donor cell lineages.     

Human cloning: can it be made safe?

There are continued claims of attempts to clone humans using nuclear transfer, despite the serious problems that have been encountered in cloning other mammals. It is known that epigenetic and genetic mechanisms are involved in clone failure, but we still do not know exactly how. Human reproductive cloning is unethical, but the production of cells from cloned embryos could offer many potential benefits. So, can human cloning be made safe?